This application proposes to establish an Oklahoma Center of Biomedical Research Excellence (COBRE) in Structural Biology. Structural biology is a multidisciplinary research area that focuses on the important relationship between macromolecular structure and function. A structural biology approach can be taken to study any area of biological science and thus it has had a major impact on both basic and applied biomedical research. At the OU-Norman and OUHSC campuses, a number of research groups utilize a structural approach to study important biological macromolecules, in particular, proteins or nucleic acids that are promising targets for rationale drug design. Because of the multidisciplinary nature of structural biology, the training of students, postdocs, and researchers new to the field can be challenging. In addition, the instrumentation required for structural biology is both expensive and sophisticated. The overall objective of this proposal is to establish an Oklahoma COBRE in Structural Biology in order to build and nurture a critical mass of researchers in this area and support their research programs through shared resources and expertise. The specific aims of this application are to: 1) Further the research activities and career development of junior investigators through senior mentorship and strengthening of research infrastructure; 2) Create state-wide core facilities in macromolecular X-ray crystallography, high throughput crystallization, and protein expression/purification, which will provide users access to shared major instrumentation, staff support and research training; and 3) Promote structural biology in the State of Oklahoma through COBRE activities such as annual symposia, workshops, a seed grant program and core research facilities. Collectively, these specific aims are expected to increase the pace, competitiveness and success rate of structural biology research groups in Oklahoma as they seek major independent external grant support.